The goals of this study are to evaluate the role of humoral and cellular (CTL) effector mechanisms in natural and induced immunity to HCV, and to achieve broadly cross reactive prophylactic immunization. Immune responses will be determined during the development of self-limited or chronic infections in HCV inoculated chimpanzees to evaluate correlates of immunity. The experiments will also evaluate a variety of HCV genomic constructs in plasmids and canary pox vectors, and E1E2 proteins, for induction of humoral and cellular immune responses in chimpanzees. Lymphokine genes (GM-CSF, IL-2 or IL-12) will be used together with HCV viral genes, to assess their efficacy in enhancement of immune responses. The humoral, CD4 T-helper and CTL responses will be analyzed quantitatively and qualitatively. The immunogenicity of HCV genes presented as fusion proteins with ubiquitin and secreting and non-secreting HCV gene-containing plasmids will be compared.